CORE SUMMARY Neuropathology Core C The Neuropathology Core (Core C) of the Johns Hopkins Udall Parkinson's Disease Research Center has three overarching goals. The first is to conduct postmortem neuropathological assessments in subjects from the Clinical Core and to distribute autopsy brain tissues for research to Projects 1, 2 & 4 and the Proteomic Core. The second is to obtain a comprehensive genetic profile of all the postmortem tissues available in the Udall Center collection. The third is to provide support for the morphological evaluation of genetically engineered mouse models by investigators in Projects 1, 2 & 4. The specific aims of Core C are as follows: (1) to arrange and perform neuropathological autopsies of cases of Parkinson's disease (PD) and Lewy body disease (LBD), and control subjects followed by the Clinical Core, and to formulate pathological diagnoses; (2) to accession, prepare, catalog, and assist in the analysis of human postmortem tissues from cases of PD/LBD and related disorders, as well as age-matched and also younger controls for studies proposed in Projects 1, 2 & 4 and the Proteomic Core; (3) to characterize the molecular genetic profiles of PD/LBD postmortem tissues available in the BRC through a collaboration with the Laboratory of Neurogenetics at NIA (A. Singleton, Ph.D.); and (4) to use CLARITY technology for preparation of mouse brain tissues in support of studies delineated in Projects 1, 2 & 4. Despite recent advances in neuroimaging postmortem brain examination remains indispensable. For accurate diagnosis of PD (Parkinson's disease) and LBD (Lewy body disease) in our experience, ~20% of cases clinically diagnosed as PD have other etiologies, and >30% of the cases have coexisting morbidities. Moreover, since autopsies are the essential source of tissues for studying molecular/biochemical abnormalities of the human brain associated with PD/LBD, a thorough pathological characterization is important before tissues can be used in studies proposed in Projects 1, 2 & 4 and by the Proteomic Core. Core C is expanding its postmortem tissue collection to include a large number of specimens from younger subjects (16 to 65 years) suitable to examine the very early stages of PD/LBD pathology and its pathogenesis. These tissues are accessioned through collaboration with the Lieber Institute for Developmental Disorders at Johns Hopkins. Finally, by using CLARITY, a state-of-the-art morphological technique implemented by Core C, investigators in Projects 1, 2 & 4 will be able to produce translucent preparations of whole mouse brains that allow interrogation of molecular events not only of single neuronal populations but of networks relevant to PD and LBD.